Social Behavior Phenotypes Research Articles

CYFIP1 overexpression increases fear response in mice but does not affect social or repetitive behavioral phenotypes

BackgroundCYFIP1, a protein that interacts with FMRP and regulates protein synthesis and actin dynamics, is overexpressed in Dup15q syndrome as well as autism spectrum disorder (ASD). While CYFIP1 heterozygosity has been rigorously studied due to its loss in 15q11.2 deletion, Prader-Willi and Angelman syndrome, the effects of CYFIP1 overexpression, as is observed in patients with CYFIP1 duplication, are less well understood.MethodsWe developed and validated a mouse model of human CYFIP1 overexpression (CYFIP1 OE) using qPCR and western blot analysis. We performed a large battery of behavior testing on these mice, including ultrasonic vocalizations, three-chamber social assay, home-cage behavior, Y-maze, elevated plus maze, open field test, Morris water maze, fear conditioning, prepulse inhibition, and the hot plate assay. We also performed RNA sequencing and analysis on the basolateral amygdala.ResultsExtensive behavioral testing in CYFIP1 OE mice reveals no changes in the core behaviors related to ASD: social interactions and repetitive behaviors. However, we did observe mild learning deficits and an exaggerated fear response. Using RNA sequencing of the basolateral amygdala, a region associated with fear response, we observed changes in pathways related to cytoskeletal regulation, oligodendrocytes, and myelination. We also identified GABA-A subunit composition changes in basolateral amygdala neurons, which are essential components of the neural fear conditioning circuit.ConclusionOverall, this research identifies the behavioral and molecular consequences of CYFIP1 overexpression and how they contribute to the variable phenotype seen in Dup15q syndrome and in ASD patients with excess CYFIP1.

Behavioral training rescues motor deficits in Cyfip1 haploinsufficiency mouse model of autism spectrum disorders

Deletions in the 15q11.2 region of the human genome are associated with neurobehavioral deficits, and motor development delay, as well as in some cases, symptoms of autism or schizophrenia. The cytoplasmic FMRP-interacting protein 1 (CYFIP1) is one of the four genes contained within this locus and has been associated with other genetic forms of autism spectrum disorders (ASD). In mice, Cyfip1 haploinsufficiency leads to alteration of dendritic spine morphology and defects in synaptic plasticity, two pathophysiological hallmarks of mouse models of ASD. At the behavioral level, however, Cyfip1 haploinsufficiency leads to minor phenotypes, not directly relevant for 15q11.2 deletion syndrome or ASD. A fundamental question is whether neuronal phenotypes caused by the mutation of Cyfip1 are relevant for the human condition. Here, we describe a synaptic cluster of ASD-associated proteins centered on CYFIP1 and the adhesion protein Neuroligin-3. Cyfip1 haploinsufficiency in mice led to decreased dendritic spine density and stability associated with social behavior and motor learning phenotypes. Behavioral training early in development resulted in alleviating the motor learning deficits caused by Cyfip1 haploinsufficiency. Altogether, these data provide new insight into the neuronal and behavioral phenotypes caused by Cyfip1 mutation and proof-of-concept for the development of a behavioral therapy to treat phenotypes associated with 15q11.2 syndromes and ASD.

Generation of a triple-fluorescent mouse strain allows a dynamic and spatial visualization of different liver phagocytes in vivo.

Resident and circulating immune cells have been extensively studied due to their almost ubiquitous role in cell biology. Despite their classification under the "immune cell department", it is becoming increasingly clear that these cells are involved in many different non-immune related phenomena, including fetus development, vascular formation, memory, social behavior and many other phenotypes. There is a huge potential in combining high-throughput assays - including flow cytometry and gene analysis - with in vivo imaging. This can improve our knowledge in both basic and clinical cell biology, and accessing the expression of markers that are relevant in the context of both homeostasis and disease conditions might be instrumental. Here we describe how we generated a novel mouse strain that spontaneously express three different fluorescence markers under control of well-studied receptors (CX3CR1, CCR2 and CD11c) that are involved in a plethora of stages of cell ontogenesis, maturation, migration and behavior. Also, we assess the percentage of the expression and co-expression of each marker under homeostasis conditions, and how these cells behave when a local inflammation is induced in the liver applying a cutting-edge technology to image cells by confocal intravital microscopy.

Assessing Sociability, Social Memory, and Pup Retrieval in Mice.

Adaptive social behavior is important in mammals, both for the well-being of the individual and for the thriving of the species. Dysfunctions in social behavior occur in many neurodevelopmental and psychiatric diseases, and research into the genetic components of disease-relevant social deficits can open up new avenues for understanding the underlying biological mechanisms and therapeutic interventions. Genetically modified mouse models are particularly useful in this respect, and robust experimental protocols are needed to reliably assess relevant social behavior phenotypes. Here we describe in detail three protocols to quantitatively measure sociability, one of the most frequently investigated social behavior phenotypes in mice, using a three-chamber sociability test. These protocols can be extended to also assess social memory. In addition, we provide a detailed protocol on pup retrieval, which is a particularly robust maternal behavior amenable to various scientific questions. © 2017 by John Wiley & Sons, Inc.

Features of emotional and social behavioral phenotypes of calsyntenin2 knockout mice.

Calsyntenin-2 (Clstn2) is the synaptic protein that belongs to the super family of cadherins, playing an important role in learning and memory. We recently reported that Clstn2 knockout mice (Clstn2-KO) have a deficit of GABAergic interneurons coupled with hyperactivity and deficient spatial memory. Given, that impaired functioning of GABA receptors is linked to several psychopathologies, including anxiety and autism, we sought to further characterize Clstn2-KO mice with respect to emotional and social behavior. Clstn2-KO males and females were tested in the elevated plus-maze (EPM), open field (OF), forced swim test, social affiliation and recognition test, social transmission of food preference (STFP), dyadic social interactions and marble burying test. Clstn2-KO mice demonstrated high exploration and hyperactivity in the dimly lit EPM that affect anxiety parameters. In contrast, in a more adverse situation in the OF have increased emotionality in Clstn2-KO males, not females. Assessment of hyperactivity for prolong period in the OF showed that Clstn2-KO animals were able to decline their hyperactivity, but their ambulation still remained higher than in WT littermates. Additionally, Clstn2-KO mice expressed stereotyped behavior. Strikingly, analysis of social behavior identified deficient social motivation and social recognition only in Clstn2-KO males, but not in females. Further analysis of social communication in the STFP and direct observation of agonistic interactions confirmed the reduced social behavior in Clstn2-KO males. Altogether, current results showed Clstn2 gene and sex interactions on socio-emotional performance in mice, suggesting a possible role of calsyntenin2 in psychopathological mechanisms of autism.

Dissecting the Transcriptional Patterns of Social Dominance across Teleosts.

In many species, under varying ecological conditions, social interactions among individuals result in the formation of dominance hierarchies. Despite general similarities, there are robust differences among dominance hierarchies across species, populations, environments, life stages, sexes, and individuals. Understanding the proximate mechanisms underlying the variation is an important step toward understanding the evolution of social behavior. However, physiological changes associated with dominance, such as gonadal maturation and somatic growth, often complicate efforts to identify the specific underlying mechanisms. Traditional gene expression analyses are useful for generating candidate gene lists, but are biased by choice of significance cut-offs and difficult to use for between-study comparisons. In contrast, complementary analysis tools allow one to both test a priori hypotheses and generate new hypotheses. Here we employ a meta-analysis of high-throughput expression profiling experiments to investigate the gene expression patterns that underlie mechanisms and evolution of behavioral social phenotypes. Specifically, we use a collection of datasets on social dominance in fish across social contexts, sex, and species. Using experimental manipulation to produce female dominance hierarchies in the cichlid Astatotilapia burtoni, heralded as a genomic model of social dominance, we generate gene lists, and assess molecular gene modules. In the dominant female gene expression profile, we demonstrate a strong pattern of up-regulation of genes previously identified as having male-biased expression and furthermore, compare expression biases between male and female dominance phenotypes. Using a threshold-free approach to identify correlation throughout ranked gene lists, we query previously published datasets associated with maternal behavior, alternative reproductive tactics, cooperative breeding, and sex-role reversal to describe correlations among these various neural gene expression profiles associated with different instances of social dominance. These complementary approaches capitalize on the high-throughput gene expression profiling from similar behavioral phenotypes in order to address the mechanisms associated with social dominance behavioral phenotypes.

Oxytocin receptor polymorphism and childhood social experiences shape adult personality, brain structure and neural correlates of mentalizing

IntroductionThe oxytocin system is involved in human social behavior and social cognition such as attachment, emotion recognition and mentalizing (i.e. the ability to represent mental states of oneself and others). It is shaped by social experiences in early life, especially by parent–infant interactions. The single nucleotid polymorphism rs53576 in the oxytocin receptor (OXTR) gene has been linked to social behavioral phenotypes. MethodIn 195 adult healthy subjects we investigated the interaction of OXTR rs53576 and childhood attachment security (CAS) on the personality traits “adult attachment style” and “alexithymia” (i.e. emotional self-awareness), on brain structure (voxel-based morphometry) and neural activation (fMRI) during an interactive mentalizing paradigm (prisoner's dilemma game; subgroup: n=163). ResultsWe found that in GG-homozygotes, but not in A-allele carriers, insecure childhood attachment is - in adulthood - associated with a) higher attachment-related anxiety and alexithymia, b) higher brain gray matter volume of left amygdala and lower volumes in right superior parietal lobule (SPL), left temporal pole (TP), and bilateral frontal regions, and c) higher mentalizing-related neural activity in bilateral TP and precunei, and right middle and superior frontal gyri. Interaction effects of genotype and CAS on brain volume and/or function were associated with individual differences in alexithymia and attachment-related anxiety. Interactive effects were in part sexually dimorphic. ConclusionThe interaction of OXTR genotype and CAS modulates adult personality as well as brain structure and function of areas implicated in salience processing and mentalizing. Rs53576 GG-homozygotes are partially more susceptible to childhood attachment experiences than A-allele carriers.

Engaging Primary Care Clinicians in Early Obesity Prevention Research.

Childhoodobesity is apublichealthproblemofglobal significance. The medical and psychosocial comorbidities of childhood obesity areextensive, and thedisorder is costly to individual childrenandsocieties.Particularlychallenging is the “tracking”ofobesity1: obese children tend to become obese adolescents, who in turn tend to become obese adults and harbor itsmanycomorbidities.Althoughthis certainly isnot trueofall obese children,environmentalandbiologicalpressurescanunderminesuccessful weight loss even among the most determined families. For these reasons, the prevention of childhood obesity is an internationalpriority.However, controlled intervention trials striving toprevent childhood obesity are scarce, and even rarer are those occurring in the first2yearsof life.Thispresentsan importantopportunity for innovativeearlyobesitypreventionstudies, guidedby recentdiscoveries of biological and behavioral mechanisms. In this context, the 2013 conference hosted by the National Institute of Diabetes and Digestive and Kidney Diseases on infancy and early obesity prevention was an important event. The resulting working group report was published in the May 2015 issue of JAMA Pediatrics.2 The report summarized what is currently known about obesity prevention in infancy and early childhood. Knowledge gaps and research needs were identified, including the need to better understand how obesity is influenced by infant weight and length (and how these relate to reference standards), infant body composition, intrauterine factors, rapid weight gain in infancy, physical activity, sleep, feeding modality (eg, bottle vs alteration in milk flow), food preferences and appetitive behavior in infants, formula and breast milk composition, complementary feeding, social cognitive variables (eg, parent or sibling behaviors), behavioral phenotypes (eg, food preferences, temperament), infant emotion and behavioral regulation, maternal feeding values and beliefs, and emerging risk factors (eg, hormonal milieu, microbiome). The report by Lumeng et al2 will stimulate new multidisciplinary research that has not been explored to date. As this process unfolds, a natural partner for collaborative research will be primary care pediatrics—ie, pediatricians, family practice physicians, nurses, and other health professionals at the clinic. (These professionals also work in many school clinics.) Primary care clinicians have long-standing relations with children, are on the front line with families, and are the authority to whom parents turn so often for guidance. Moreover, primary care is rapidly becoming a pivotal repository for “big data” collection about patients—ie, electronic medical records (EMRs). For this and other reasons, primary care clinicians should be considered invested stakeholders in advancing the research agenda of the National Institutes of Health (NIH) working group. As theNIHdevelops a strategy for investigating childhoodobesity, how can primary care clinicians contribute? The overall research effort should capitalize on interventions that can already be implementedbyprimary care clinicians. A recent reviewofprimary care interventions for childhoodobesitydispels thenotion that this intervention is not effective. Overweight or obese children treated inaprimary care settingorwithhelp fromaprimaryhealth careprofessional showed significant improvements compared with controls foranthropometric,metabolic,andbehavioraloutcomes.3Studies of primary care interventions for obesity, in general, are limited bysmall sample sizes, lack follow-upassessment, anddiffer inmethodological rigor, highlighting the need for further research. Results from a family-based behavioral intervention conductedat4 largeurban/suburbanpractices inNewYorkareencouraging, with 105 families randomized to treatment.4 Children assignedtoreceivefamily interventioncomparedwithcontrolachieved JAMA Patient Page page 850 JAMAPEDIATRICS

Natal dispersal in a social landscape: Considering individual behavioral phenotypes and social environment in dispersal ecology

Abstract Natal dispersal, the movement of an organism from its birthplace to the site of first reproduction, is fundamental to many ecological and evolutionary processes. Mechanistically, individual dispersal decisions can depend on both individual phenotype and environmental cues. In particular, many established evolutionary theories of dispersal highlight the importance of the social environment. More recent research in behavioral ecology has focused on the importance of individual behavioral phenotypes. We reviewed the literature on individual behavioral phenotypes and dispersal and suggest that how individual behavioral phenotypes interact with the immediate social environment experienced by individuals in influencing dispersal is still poorly understood, despite growing interest. We found that very few studies had examined the interaction of individual behavioral phenotypes and social factors, and behavioral phenotypes related to social tendencies were less commonly measured than were behavioral phenotypes related to exploration or response to risk. Further, and unsurprisingly, studies on social behavioral phenotypes and dispersal behaviors during the transience stage of dispersal were underrepresented compared to the departure or settlement stages. Future studies in this area should aim to: a) make explicit links between behavioral traits and their proposed effects on dispersal decisions throughout multiple stages of dispersal, b) integrate more continuous dispersal variables, and c) consider the effects of the spatial distribution and phenotypes of conspecifics (i.e., the social landscape) encountered by individual dispersers.

Transmission Disequilibrium of Small CNVs in Simplex Autism

We searched for disruptive, genic rare copy-number variants (CNVs) among 411 families affected by sporadic autism spectrum disorder (ASD) from the Simons Simplex Collection by using available exome sequence data and CoNIFER (Copy Number Inference from Exome Reads). Compared to high-density SNP microarrays, our approach yielded ∼2× more smaller genic rare CNVs. We found that affected probands inherited more CNVs than did their siblings (453 versus 394, p = 0.004; odds ratio [OR] = 1.19) and that the probands' CNVs affected more genes (921 versus 726, p = 0.02; OR = 1.30). These smaller CNVs (median size 18 kb) were transmitted preferentially from the mother (136 maternal versus 100 paternal, p = 0.02), although this bias occurred irrespective of affected status. The excess burden of inherited CNVs among probands was driven primarily by sibling pairs with discordant social-behavior phenotypes (p < 0.0002, measured by Social Responsiveness Scale [SRS] score), which contrasts with families where the phenotypes were more closely matched or less extreme (p > 0.5). Finally, we found enrichment of brain-expressed genes unique to probands, especially in the SRS-discordant group (p = 0.0035). In a combined model, our inherited CNVs, de novo CNVs, and de novo single-nucleotide variants all independently contributed to the risk of autism (p < 0.05). Taken together, these results suggest that small transmitted rare CNVs play a role in the etiology of simplex autism. Importantly, the small size of these variants aids in the identification of specific genes as additional risk factors associated with ASD.

The Social Behavioral Phenotype in Boys and Girls with an Extra X Chromosome (Klinefelter Syndrome and Trisomy X): A Comparison with Autism Spectrum Disorder

The present study aimed to gain more insight in the social behavioral phenotype, and related autistic symptomatology, of children with an extra X chromosome in comparison to children with ASD. Participants included 60 children with an extra X chromosome (34 boys with Klinefelter syndrome and 26 girls with Trisomy X), 58 children with ASD and 106 controls, aged 9 to 18years. We used the Autism Diagnostic Interview, Social Responsiveness Scale, Social Anxiety Scale and Social Skills Rating System. In the extra X group, levels of social dysfunction and autism symptoms were increased, being in between controls and ASD. In contrast to the ASD group, the extra X group showed increased social anxiety. The effects were similar for boys and girls with an extra X chromosome.

Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome

The overarching goal of this review is to compare and contrast the cognitive-behavioral features of fragile X syndrome (FraX) and Williams syndrome and to review the putative neural and molecular underpinnings of these features. Information is presented in a framework that provides guiding principles for conceptualizing gene-brain-behavior associations in neurodevelopmental disorders. Abnormalities, in particular cognitive-behavioral domains with similarities in underlying neurodevelopmental correlates, occur in both FraX and Williams syndrome including aberrant frontostriatal pathways leading to executive function deficits, and magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal lobe, and postcentral gyrus abnormalities contributing to deficits in visuospatial function. Compelling cognitive-behavioral and neurodevelopmental contrasts also exist in these two disorders, for example, aberrant amygdala and fusiform cortex structure and function occurring in the context of contrasting social behavioral phenotypes, and temporal cortical and cerebellar abnormalities potentially underlying differences in language function. Abnormal dendritic development is a shared neurodevelopmental morphologic feature between FraX and Williams syndrome. Commonalities in molecular machinery and processes across FraX and Williams syndrome occur as well - microRNAs involved in translational regulation of major synaptic proteins; scaffolding proteins in excitatory synapses; and proteins involved in axonal development. Although the genetic variations leading to FraX and Williams syndrome are different, important similarities and contrasts in the phenotype, neurocircuitry, molecular machinery, and cellular processes in these two disorders allow for a unique approach to conceptualizing gene-brain-behavior links occurring in neurodevelopmental disorders.

A multimeasure approach to investigating affective appraisal of social information in Williams syndrome

People with Williams syndrome (WS) have been consistently described as showing heightened sociability, gregariousness, and interest in people, in conjunction with an uneven cognitive profile and mild to moderate intellectual or learning disability. To explore the mechanisms underlying this unusual social–behavioral phenotype, we investigated whether individuals with WS show an atypical appraisal style and autonomic responsiveness to emotionally laden images with social or nonsocial content. Adolescents and adults with WS were compared to chronological age-matched and nonverbal mental age-matched groups in their responses to positive and negative images with or without social content, using measures of self-selected viewing time (SSVT), autonomic arousal reflected in pupil dilation measures, and likeability ratings. The participants with WS looked significantly longer at the social images compared to images without social content and had reduced arousal to the negative social images compared to the control groups. In contrast to the comparison groups, the explicit ratings of likeability in the WS group did not correlate with their SSVT; instead, they reflected an appraisal style of more extreme ratings. This distinctive pattern of viewing interest, likeability ratings, and autonomic arousal to images with social content in the WS group suggests that their heightened social drive may be related to atypical functioning of reward-related brain systems reflected in SSVT and autonomic reactivity measures, but not in explicit ratings.

Epilepsy and Tsc2 Haploinsufficiency Lead to Autistic-Like Social Deficit Behaviors in Rats

There is a strong association between autism spectrum disorders (ASD), epilepsy and intellectual disability in humans, but the nature of these correlations is unclear. The monogenic disorder Tuberous Sclerosis Complex (TSC) has high rates of ASD, epilepsy and cognitive deficits. Here we used the Tsc2 (+/-) (Eker) rat model of TSC and an experimental epilepsy paradigm to study the causal effect of seizures on learning and memory and social behavior phenotypes. Status epilepticus was induced by kainic acid injection at P7 and P14 in wild-type and Tsc2 (+/-) rats. At the age of 3-6months, adult rats were assessed in the open field, light/dark box, fear conditioning, Morris water maze, novel object recognition and social interaction tasks. Learning and memory was unimpaired in naïve Tsc2 (+/-) rats, and experimental epilepsy did not impair any aspects of learning and memory in either wild-type or Tsc2 (+/-) rats. In contrast, rearing in the open field, novel object exploration and social exploration was reduced in naïve Tsc2 (+/-) rats. Seizures induced anxiety and social evade, and reduced social exploration and social contact behavior in wild-type and Tsc2 (+/-) rats. Our study shows that Tsc2 haploinsufficiency and developmental status epilepticus in wild-type and Tsc2 (+/-) rats independently lead to autistic-like social deficit behaviors. The results suggest that the gene mutation may be sufficient to lead to some social deficits, and that seizures have a direct and additive effect to increase the likelihood and range of autistic-like behaviors.

A common allele in the oxytocin receptor gene ( OXTR ) impacts prosocial temperament and human hypothalamic-limbic structure and function

The evolutionarily highly conserved neuropeptide oxytocin is a key mediator of social and emotional behavior in mammals, including humans. A common variant (rs53576) in the oxytocin receptor gene (OXTR) has been implicated in social-behavioral phenotypes, such as maternal sensitivity and empathy, and with neuropsychiatric disorders associated with social impairment, but the intermediate neural mechanisms are unknown. Here, we used multimodal neuroimaging in a large sample of healthy human subjects to identify structural and functional alterations in OXTR risk allele carriers and their link to temperament. Activation and interregional coupling of the amygdala during the processing of emotionally salient social cues was significantly affected by genotype. In addition, evidence for structural alterations in key oxytocinergic regions emerged, particularly in the hypothalamus. These neural characteristics predicted lower levels of reward dependence, specifically in male risk allele carriers. Our findings identify sex-dependent mechanisms impacting the structure and function of hypothalamic-limbic circuits that are of potential clinical and translational significance.

Male mating preference is associated with risk of pre-copulatory cannibalism in a socially polymorphic spider

We performed male attraction experiments and staged courtship sequences to test for non-random mating with respect to social behavioral phenotype in the comb-footed spider, Anelosimus studiosus. While asocial behavior is the dominant phenotype in all A. studiosus populations examined to date, a social phenotype approaches a frequency of 15% in colder environments. We collected test subjects from higher latitude polymorphic populations and scored all individuals as to their behavioral phenotype prior to their use in these trials. Males of both phenotypes differentially approached and courted social females over asocial females and no-spider controls. By offering males different numbers of females of one type vs. the other in subsequent trials, we determined that the difference in attractiveness between the two phenotypes social/asocial is 1.5/1. Both the web produced by a female and a female that has been removed from its web attract males. We suggest that the male attracting pheromone is present on females and is also attached to silk threads. Staged encounters completed between males and females of the respective phenotypes demonstrated that courting males suffer significantly less pre-copulatory sexual cannibalism with social females than with asocial ones, and thus, female social tendency is phenotypically linked to sexual aggression. We propose that the male preference for social females is adaptive because of the observed asymmetry in courtship success.

The social behavior of male rats administered an adult-onset calorie restriction regimen

The behavioral outcomes of a calorie restricted diet are often neglected in favour of a more physiological examination of the consequences of calorie restriction (CR). This is especially the case with social behavior. A few findings within the maternal CR literature suggest that adult male social behavior is altered by this regimen. Despite the paucity of findings within the maternal CR literature, a systematic investigation of the behavioral phenotype of males administered an adult-onset CR is completely lacking and was the focus of the current study. Adult male hooded Wistar rats were administered a three week CR, with one group receiving a 25% CR and another group receiving a 50% CR before male-to-male social behavior was examined and compared with ad libitium fed males. Various behavioral elements were modulated by CR, both the CR25% and 50% group initiated contact sooner and engaged in greater social activity compared to the ad libitum fed controls. The CR25% group also demonstrated less non-social (self-grooming) behavior and a greater frequency of walkovers compared to all groups, indicating a propensity towards dominance. The CR50% group demonstrated greater environmental assessment/exploration, as measured by the frequency of rearing. As with the maternal CR literature, an adult-onset chronic CR induces a more socially active behavioral phenotype and reduces interest in non-social behavior in the moderately CR group. Taken together, the social behavioral phenotype can be modulated by a CR initiated and maintained during adulthood.

Testosterone, social and sexual behavior of perinatally and lifelong calorie restricted offspring

Calorie restriction (CR) during sensitive perinatal periods has consistently been demonstrated to alter the development of a variety of physiological systems, which consequently affect behavior. This study compared the social behavior and sexual behavior of the adult male offspring of mothers administered a 25% CR at one of four times in the perinatal period: a brief period preconception, during gestation, during lactation, or a lifelong restriction (beginning at conception and continuing throughout life). Levels of serum testosterone were also determined in these animals. Social interaction increased in the gestation and lifelong CR groups. The lifelong group also exhibited more dominant type behaviors. CR during preconception and lactation resulted in offspring that displayed an enhanced and more efficient copulatory pattern compared to all other conditions. This was demonstrated by a reduced frequency of intromissions, shorter latency to ejaculation, and a greater frequency of ejaculations by the preconception and lactation group compared to some, if not all of the other CR groups and controls. Serum testosterone was significantly higher in the preconception group compared to controls. These findings indicate that CR during specific periods of development can differentially alter the social behavioral phenotype and hormone levels in adulthood.

Social Behavior and Autism Traits in a Sex Chromosomal Disorder: Klinefelter (47XXY) Syndrome

Although Klinefelter syndrome (47,XXY) has been associated with psychosocial difficulties, knowledge of the social behavioral phenotype is limited. We examined specific social abilities and autism traits in Klinefelter syndrome. Scores of 31 XXY men on the Scale for Interpersonal Behavior and the Autism Spectrum Questionnaire were compared to 24 and 20 control men respectively. XXY men reported increased distress during social interactions and less engagement in specific social behaviors. In the XXY group, levels of autism traits were significantly higher across all dimensions of the autism phenotype. These findings call for a clinical investigation of vulnerability to autism in Klinefelter syndrome. Klinefelter syndrome might serve as a model for studying a role of the X chromosome in social behavioral dysfunction and autism-like behavior.

Social behavior phenotypes in fragile X syndrome, autism, and the Fmr1 knockout mouse: Theoretical comment on McNaughton et al. (2008).

Comments on the article by C. H. McNaughton et al.. Individuals with fragile X syndrome (FXS) show varying degrees of social behavior disturbances, from social anxiety to autism. This variability of social behavior phenotypes in FXS is likely to be due to interactions of Fmr1 with other gene variants and environmental factors during brain development, although very little is known about the specific genetic and neural mechanisms involved. The Fmr1 knockout mouse is an important experimental resource for elucidating the neural mechanisms of social anxiety, social reward, and social cognition. However, studies of social behavior phenotypes in the Fmr1 knockout mouse are still in early stages. McNaughton et al provide important new information on these phenotypes in the Fmr1 knockout mouse through their use of novel, detailed behavioral analysis to identify signs of increased social anxiety and social cognition deficits. Their significant refinements in measurement of social behavior phenotypes will help to advance future efforts to elucidate the genetic and neural mechanisms underlying social behavior disturbances in FXS and autism.